Treatment of Advanced Emphysema with Emphysematous Lung Sealant (AeriSeal (R))

Background: This report summarizes initial tests of an emphysematous lung synthetic polymer sealant (ELS) designed to reduce lung volume in patients with advanced emphysema. Objectives: The primary study objective was to define a therapeutic strategy to optimize treatment safety and effectiveness. Methods: ELS therapy was administered bronchoscopically to 25 patients with heterogeneous emphysema in an open-label, noncontrolled study at 6 centers in Germany. Treatment was performed initially at 2-4 subsegments. After 12 weeks, patients were eligible for repeat therapy to a total of 6 sites. Safety and efficacy were assessed after 6 months. Responses were evaluated in terms of changes from baseline in lung physiology, functional capacity, and health-related quality of life. Follow-up is available for 21 of 25 patients. Results: Treatment was well tolerated. There were no treatment-related deaths (i.e. within 90 days of treatment), and an acceptable short-and long-term safety profile. Physiological and clinical benefits were observed at 24 weeks. Efficacy responses were better among Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage III patients {[}n = 14; change in residual volume/total lung capacity (Delta RV/TLC) = -7.4 +/- 10.3%; Delta forced expiratory volume in 1 s (Delta FEV(1)) = +15.9 +/- 22.6%; change in forced vital capacity (Delta FVC) = +24.1 +/- 22.7%; change in carbon monoxide lung diffusion capacity (Delta DLCO) = +19.3 +/- 34.8%; change in 6-min walk test (Delta 6MWD) = +28.7 +/- 59.6 m; change in Medical Research Council Dyspnea (Delta MRCD) score = -1.0 +/- 1.04 units; change in St. George's Respiratory Questionnaire (Delta SGRQ) score = -9.9 +/- 15.3 units] than for GOLD stage IV patients (n = 7; Delta RV/TLC = -0.5 +/- 6.4%; Delta FEV 1 = +2.3 +/- 12.3%; Delta FVC = +2.6 +/- 21.1%; Delta DLCO = -2.8 +/- 17.2%; Delta 6MWD = +28.3 +/- 58.4 m; Delta MRCD = 0.3 +/- 0.81 units; Delta SGRQ = -6.7 +/- 7.0 units). Conclusions: ELS therapy shows promise for treating patients with advanced heterogeneous emphysema. Additional studies to assess responses in a larger cohort with a longer follow-up are warranted. Copyright (C) 2011 S. Karger AG, Base

Osteoporosis prevention in postmenopausal female workers : Beneficial effects of silicon dietary supplementation on oxidative status. A pilot study

In the last years, the employment of ageing women is increased, and the well-being of these workers, together with the prevention of chronic disabling diseases, is an issue of great importance. Moreover, as postmenopausal ageing is associated with the loss of bone density and consequent increased fracture risk, promoting bone health in these women could be the best strategy for avoiding osteoporotic fractures. We aimed to evaluate the effects of 3-month supplementation with a commercial antioxidant product containing Silica on oxidative status and bone markers in a sample of Italian female workers. Subjects were menopausal and osteopenic women (N=29, age 59.34\ub16.37, mean BMI 26.19\ub14.01 kg/m2). At baseline (T0) and after three-month treatment (T1) bone mineral density (BMD) was evaluated by phalangeal osteosonogrammetry. Haematological, serum biochemical parameters, reactive oxygen species (ROS), total antioxidant capacity (TAC), oxydated low-density lipoproteins (oxLDL) and urinary cross-links pyridinoline (PYD) and deoxypyridinoline (DPD) were assessed. Parametric or non-parametric tests were performed at T0 and T1. To analyse the possible association between two variables a linear correlation test was performed. At T0, slightly high levels of ROS (86% of subjects), oxLDL (59%), Total Cholesterol (T-Chol) (90%) and LDL-Chol (59%) were observed, together with suboptimal or deficient 25-OH vitamin D (98%) concentrations. At T1, oxLDL levels and the ratio oxLDL/LDL-Chol significantly decreased (p<0.01). At T0 significant negative correlations between BMD T-score and cross-links were observed (DPD/Crea: r=-0.57, p=0.001; PYD/ Crea: r=-0.45, p=0.01). At T1, a significant reduction (p=0.03) was observed only for DPD (\u3bcg/L) but not for cross-links normalized by creatinine amounts. In conclusion 3-months Silica supplementation improves significantly oxidative status and bone resorption markers in most postmenopausal female workers, representing a complementary treatment for early phases of BMD reduction

Age-Dependent Decline in Mouse Lung Regeneration with Loss of Lung Fibroblast Clonogenicity and Increased Myofibroblastic Differentiation

While aging leads to a reduction in the capacity for regeneration after pneumonectomy (PNX) in most mammals, this biological phenomenon has not been characterized over the lifetime of mice. We measured the age-specific (3, 9, 24 month) effects of PNX on physiology, morphometry, cell proliferation and apoptosis, global gene expression, and lung fibroblast phenotype and clonogenicity in female C57BL6 mice. The data show that only 3 month old mice were fully capable of restoring lung volumes by day 7 and total alveolar surface area by 21 days. By 9 months, the rate of regeneration was slower (with incomplete regeneration by 21 days), and by 24 months there was no regrowth 21 days post-PNX. The early decline in regeneration rate was not associated with changes in alveolar epithelial cell type II (AECII) proliferation or apoptosis rate. However, significant apoptosis and lack of cell proliferation was evident after PNX in both total cells and AECII cells in 24 mo mice. Analysis of gene expression at several time points (1, 3 and 7 days) post-PNX in 9 versus 3 month mice was consistent with a myofibroblast signature (increased Tnc, Lox1, Col3A1, Eln and Tnfrsf12a) and more alpha smooth muscle actin (αSMA) positive myofibroblasts were present after PNX in 9 month than 3 month mice. Isolated lung fibroblasts showed a significant age-dependent loss of clonogenicity. Moreover, lung fibroblasts isolated from 9 and 17 month mice exhibited higher αSMA, Col3A1, Fn1 and S100A expression, and lower expression of the survival gene Mdk consistent with terminal differentiation. These data show that concomitant loss of clonogenicity and progressive myofibroblastic differentiation contributes to the age-dependent decline in the rate of lung regeneration

Study on a compact and adaptable Thomson Spectrometer for laser-initiated 11B(p,α)8Be reactions and low-medium energy particle detection

Thomson Spectrometers are of primary importance in the discrimination of particles produced by laser-plasma interaction, according to their energy and charge-mass ratio. We describe here a detailed study on a set of Thomson Spectrometers, adaptable to different experimental situations, with the aim of being placed directly within the experimental chamber, rather than in additional extensions, in order to increase the solid angle of observation. These instruments are suitable for detection of low-medium energy particles and can be effectively employed in laser-plasma experiments of 11B(p,α)8Be fusion. They are provided with permanent magnets, have small dimensions and compact design. In these small configurations electric and magnetic fringing fields play a primary role for particle deflection, and their accurate characterization is required. It was accomplished by means of COMSOL electromagnetic solver coupled to an effective analytical model, very suitable for practical use of the spectrometers. Data from experimental measurements of the magnetic fields have been also used. We describe the application of the spectrometers to an experiment of laser-plasma interaction, coupled to Imaging Plate detectors. Data analysis for spectrum and yield of the detected radiation is discussed in detail. © 2016 ENEA

Influence of emphysema distribution on pulmonary function parameters in COPD patients

Objective: To evaluate the impact that the distribution of emphysema has on clinical and functional severity in patients with COPD. Methods: The distribution of the emphysema was analyzed in COPD patients, who were classified according to a 5-point visual classification system of lung CT findings. We assessed the influence of emphysema distribution type on the clinical and functional presentation of COPD. We also evaluated hypoxemia after the six-minute walk test (6MWT) and determined the six-minute walk distance (6MWD). Results: Eighty-six patients were included. The mean age was 65.2 ± 12.2 years, 91.9% were male, and all but one were smokers (mean smoking history, 62.7 ± 38.4 pack-years). The emphysema distribution was categorized as obviously upper lung-predominant (type 1), in 36.0% of the patients; slightly upper lung-predominant (type 2), in 25.6%; homogeneous between the upper and lower lung (type 3), in 16.3%; and slightly lower lung-predominant (type 4), in 22.1%. Type 2 emphysema distribution was associated with lower FEV1 , FVC, FEV1 /FVC ratio, and DLCO. In comparison with the type 1 patients, the type 4 patients were more likely to have an FEV1 < 65% of the predicted value (OR = 6.91, 95% CI: 1.43-33.45; p = 0.016), a 6MWD < 350 m (OR = 6.36, 95% CI: 1.26-32.18; p = 0.025), and post-6MWT hypoxemia (OR = 32.66, 95% CI: 3.26-326.84; p = 0.003). The type 3 patients had a higher RV/TLC ratio, although the difference was not significant. Conclusions: The severity of COPD appears to be greater in type 4 patients, and type 3 patients tend to have greater hyperinflation. The distribution of emphysema could have a major impact on functional parameters and should be considered in the evaluation of COPD patients